An essential goal of our work is the isolation of DNA repair deficient fly strains. Signficant progress is being made towards obtaining flies lacking Rrp1 protein, a Drosophila repair enzyme with a putative major role in repair of alkylation and oxidative DNA damage. The Rrp1 gene was located in the cytogenetic interval 23C3-23E3 by deficiency mapping. Mutagenesis screens using these deficiencies have been designed to select Rrp1 mutants using two possible phenotypes: female sterility or mutagen senstivity during pupal stage. A synthetic Rrp1 mutant that expresses antisense Rrp1 mRNA is also being constructed by P-element mediated fly transformation. Overexpression fly strains expressing wild-type Rrp1 under the control of a heat-inducible promoter are being used to characterize the role of Rrp1 in the repair of mutagen-induced DNA damage in somatic tissue. Female flies induced approximately 15-fold for Rrp1 protein prior to mutagen treatment during larval development show an approximately 2-fold reduction in somatic mutation induced by gamma-irradiation, bleomycin or paraquat, but no change in MMS-induced mutation levels. This system will help define the role of Rrp1 in repair of DNA damage in vivo (manuscript in preparation). These results were presented at the 1995 Drosophila Research Conference in Atlanta, Georgia (Szakmary, Huang and Sander, 1995).